2-Decarboxy-2-alkylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-11-deoxy-PGF1 compounds

ABSTRACT

The present invention provides novel prostaglandin analogs wherein the C-2 carboxyl is replaced by alkylcarbonyl, i.e., a C-2 ketone. These novel 2-decarboxy-2-alkylcarbonyl-PG-type compounds are disclosed as improved gastrointestinal cytoprotective agents, being devoid or substantially devoid of other prostaglandin-type effects (e.g., smooth muscle or cardiovascular).

The present application is a divisional application of Ser. No. 888,695,filed Mar. 21, 1978, now U.S. Pat. No. 4,123,463.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,123,463.

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is##STR2## wherein R₁ is alkyl of one to 4 carbon atoms, inclusive;WHEREIN L₁ is ##STR3## A MIXTURE OF ##STR4## wherein R₃ and R₄ arehydrogen, methyl, or fluoro, being the same or different, with theproviso that one of R₃ and R₄ is methyl only when the other is hydrogenor methyl;Wherein M₁ is ##STR5## wherein R₅ is hydrogen or methyl;WHEREIN R₇ is(1) --(CH₂)_(m) --CH₃, ##STR6## WHEREIN H IS ZERO TO THREE,INCLUSIVE, WHEREIN M IS ONE TO 5, INCLUSIVE, S IS ZERO, ONE, 2, OR 3 ANDT is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms oralkoxy of one to 3 carbon atoms, the various T's being the same ordifferent, with the proviso that not more than two T's are other thanalkyl; Wherein Y₁ is(1) trans--CH═CH-- (2) cis--CH═CH-- (3) --ch₂ ch₂--, or (4) --C.tbd.C--; and Wherein Z₁ is ##STR7## WHEREIN G IS ONE, TWOOR THREE.
 2. A prostaglandin analog according to claim 1, wherein R₁ ismethyl.
 3. A prostaglandin analog according to claim 2, wherein D is##STR8## 4.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-11-deoxy-8β,12α-PGF₂α, a prostaglandin analog according to claim
 3. 5. A prostaglandinanalog according to claim 2, wherein D is ##STR9## 6.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-11-deoxy-PGF₂β, a prostaglandin analog according to claim
 5. 7. A prostaglandinanalog according to claim 2, wherein D is ##STR10## 8.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-11-deoxy-8β,12α-PGF₂β, a prostaglandin analog according to claim
 7. 9. A prostaglandinanalog accoridng to claim 2, wherein D is ##STR11##
 10. A prostaglandinanalog according to claim 9, wherein Y₁ is cis--CH═CH--. 11.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-13-cis-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 10. 12. A prostaglandinanalog according to claim 9, wherein Y₁ is --CH₂ CH₂ --. 13.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-13,14-dihydro-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 12. 14. A prostaglandinanalog according to claim 9, wherein Y₁ is --C.tbd.C--. 15.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-13,14-didehydro-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 14. 16. A prostaglandinanalog according to claim 9, wherein Y₁ is trans--CH.tbd.CH--.
 17. Aprostaglandin analog according to claim 16, wherein R₇ is ##STR12## 18.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-18,19,20-hexanor-17-phenyl-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 17. 19. A prostaglandinanalog according to claim 16, wherein R₇ is ##STR13## 20.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-17,18,19,20-heptanor-16-phenoxy-11-deoxy-PGF₁60 , a prostaglandin analog according to claim
 19. 21. A prostaglandinanalog according to claim 19, wherein R₇ is (CH₂)_(m) --CH₃ --.
 22. Aprostaglandin analog according to claim 21, wherein Z₁ is ##STR14## 23.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-4,5,6-trinor-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 22. 24. A prostaglandinanalog according to claim 21, wherein Z₁ is ##STR15##
 25. Aprostaglandin analog according to claim 21, wherein R₅ is methyl. 26.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-15-methyl-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 21. 27. A prostaglandinanalog according to claim 21, wherein R₅ is hydrogen.
 28. Aprostaglandin analog according to claim 27, wherein one of R₃ and R₄ isfluoro. 29.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-16,16-difluoro-11-deoxy-PGF₁α, a prostaglandin analog according to claim
 28. 30. A prostaglandinanalog according to claim 27, wherein at least one of R₃ and R₄ ismethyl. 31.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-16,16-dimethyl-11-deoxy-PGF.sub.1α, a prostaglandin analog according to claim
 30. 32. A prostaglandinanalog according to claim 27, wherein R₃ and R₄ are both hydrogen. 33.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-11-deoxy-PGF₁α, a prostaglandin analog according to claim 32.